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Salinomycin selectively targets 'CD133+' cell subpopulations and decreases malignant traits in colorectal cancer
Tao-Tao Dong1, Hou-Min Zhou, Lin-Lin Wang
1Department of Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, People's Republic of China.
Background:
Cancer stem-like cells (CSCs) in colorectal cancers (CRC) may account for the failure of treatments because they are resistant to many current anticancer therapies. Salinomycin, a potassium ionophore, was recently identified as a selective inhibitor of breast CSCs.
Methods:
The human CRC cell lines HT29 and SW480 were treated with salinomycin and oxaliplatin. Cell viability was determined with cell counting kit 8. Fraction of CD133+ cell subpopulations was assessed by Flow Cytometric analysis. Clonogenecity and migration were determined with soft agar and Boyden chamber assays. Molecular changes were assessed by immunofluorescence staining, RT-PCR, and Western blot analysis.
Results:
We report that salinomycin reduces the proportion of CD133+ subpopulations in human CRC HT29 and SW480 cells. Furthermore, salinomycin treatment decreases colony-forming ability and cell motility in HT29 cells. Moreover, salinomycin downregulates the expression of vimentin and induces the E-cadherin expression in HT29 cells.
Conclusions:
This study demonstrates the ability of salinomycin to selectively target "CD133+" cell subpopulations and decrease the malignant traits in colorectal cancer lines.
Insights
Salinomycin effectively targets cancer stem-like cells (CSCs) in colorectal cancer (CRC), reducing their proportion and decreasing malignant traits. This offers a potential new strategy for CRC treatment by overcoming therapy resistance.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Stem Cell Research
Background:
- Colorectal cancer (CRC) treatment failure is often linked to therapy-resistant cancer stem-like cells (CSCs).
- Salinomycin, a potassium ionophore, has shown selective inhibition of breast CSCs.
Purpose of the Study:
- To investigate the efficacy of salinomycin in targeting CSCs in colorectal cancer.
- To evaluate the impact of salinomycin on CSC subpopulations and malignant characteristics in CRC cell lines.
Main Methods:
- Human CRC cell lines (HT29, SW480) were treated with salinomycin and oxaliplatin.
- Assessed cell viability, CD133+ cell subpopulations, clonogenicity, migration, and molecular changes (vimentin, E-cadherin).
Main Results:
- Salinomycin reduced the proportion of CD133+ subpopulations in HT29 and SW480 cells.
- Salinomycin decreased colony formation and cell motility in HT29 cells.
- Salinomycin downregulated vimentin and upregulated E-cadherin expression in HT29 cells.
Conclusions:
- Salinomycin selectively targets CD133+ subpopulations in colorectal cancer.
- Salinomycin reduces malignant traits in colorectal cancer cell lines, suggesting therapeutic potential.
